Concomitant administration of resveratrol and insulin protects against diabetes mellitus type-1-induced renal damage and impaired function via an antioxidant-mediated mechanism and up-regulation of Na+/K+-ATPase

Abstract

This study investigated if a combination of resveratrol (RES) and insulin could reverse type 1 diabetic mellitus-induced (T1DM) nephropathy and illustrates mechanism of action. Rats were divided into six groups (n = 10/group) as follows: control, control + RES (20 mg/kg), T1DM, T1DM + RES, T1DM + insulin (1 U/g), and T1DM + RES + insulin and treated for eight weeks. While individual administrations of both drugs significantly but partially restored renal function and cortex architectures, combination therapy of both RES and insulin produced the maximum improvements. Mechanism of actions revealed a synergist effect of both drugs due to hypoglycaemic effect of insulin and the ability of both drugs to increase renal cortex antioxidant enzymes activities, inhibit lipid peroxidation, and up-regulate Na⁺/K⁺-ATPase, independent of each others. In conclusion, these data suggest the combined therapy with insulin and RES could provide an excellent combined drug therapy against T1DM-induced nephropathy.

Keywords: Na/K-ATPase; Resveratrol; diabetes; kidney; oxidative stress.